The EU Clinical Trials Register currently displays
33931
clinical trials with a EudraCT protocol, of which
5497
are clinical trials conducted with subjects less than 18 years old.
The register also displays information on
18700
older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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Assess the safety and tolerability, including determination of the maximum tolerated dose (MTD) of oral ASP2215 in subjects with relapsed or treatment-refractory AML.
Determine the pharmacokinetic (PK) parameters of ASP2215.

E.2.2

Secondary objectives of the trial

Investigate the anti-leukemic activity of various doses of ASP2215 in subjects with AML.
Evaluate the effect of strong or moderate cytochrome P450-isozyme3A4 (CYP3A4) inhibitors on the PK of ASP2215.
Evaluate the potential induction of CYP3A4 by ASP2215 by assessment of midazolam PK.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Pharmacogenetic sub-study.

E.3

Principal inclusion criteria

1) Subject is ≥18 years of age at the time of obtaining informed consent.
2) Subject is defined as morphologically documented primary or secondary AML by the World Health Organization (WHO) criteria (2008) and fulfills one of the followings:
• Refractory to at least 1 cycle of induction chemotherapy
• Relapsed after achieving remission with a prior therapy
3) Subject has an Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
4) Subject’s interval from prior treatment to time of study drug administration is at least 2 weeks for cytotoxic agents (except hydroxyurea given for controlling blast cells), or at least 5 half-lives for prior experimental agents or noncytotoxic agents, including immunosuppressive therapy post hematopoietic stem cell transplantation (HSCT).
5) Subject must meet the following criteria as indicated on the clinical laboratory tests.
• Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x institutional upper limit normal (ULN)
• Total serum bilirubin ≤1.5 x institutional ULN
• Serum creatinine ≤1.5 x institutional ULN or an estimated glomerular filtration rate (eGFR) of > 50 ml/min as calculated by the Modification of Diet in Renal Disease (MDRD) equation.

E.4

Principal exclusion criteria

1. Subject was diagnosed as acute promyelocytic leukemia (APL).
2. Subject has BCR-ABL-positive leukemia (chronic myelogenous leukemia in blast crisis).
3. Subject has active malignant tumors other than AML or Myelodysplastic Syndrome (MDS).
4. Subject has persistent non-hematological toxicities of≥ Grade 2 (CTC AE v4), with symptoms and objective findings, from prior AML treatment (including chemotherapy, kinase inhibitors, immunotherapy, experimental agents, radiation, or surgery).
5. Subject has had hematopoietic stem cell transplant (HSCT) and meets any of the following:
• Is within 2 months of transplant from C1D1
• Has clinically significant graft-versus-host disease requiring treatment
• Has ≥ Grade 2 persistent non-hematological toxicity related to the transplant
Donor lymphocytes infusion (DLI) is not permitted ≤ 30 days prior to study registration or during the first cycle of treatment on the study in Cohort 1 and first two cycles of the treatment in Cohort 2.
6. Subject has clinically active central nervous system leukemia.
7. Subject has disseminated intravascular coagulation abnormality (DIC).
8. Subject has had major surgery within 4 weeks prior to the first study dose.
9. Subject has had radiation therapy within 4 weeks prior to the first study dose.
10. Subject has congestive heart failure NYHA class 3 or 4, or subject with a history of congestive
heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram performed within
3 months prior to study entry results in a left ventricular ejection fraction that is ≥ 45%.
11. Subject with mean Fridericia-corrected QT interval (QTcF) > 450 ms
at Screening based on central reading.
12. Subject with Long corrected QT interval (QTc) Syndrome at
Screening.
13. Subject with hypokalemia and hypomagnesemia at Screening
(defined as values below lower limit of normal [LLN]).
14. Subject requires treatment with concomitant drugs that are strong
inhibitors or inducers of CYP3A4 or of P-glycoprotein (P-gp) or
substrates of multidrug and toxin extrusion 1 (MATE 1) with the
exception of antibiotics, antifungals, and antivirals that are used as
standard of care post-transplant or to prevent or treat infections and
other such drugs that are considered absolutely essential for the care of
the subject.
15. Subject requires treatment with concomitant drugs that target serotonin 5HT1R or 5HT2BR
receptors or sigma nonspecific receptor with the exception of drugs that are considered absolutely
essential for the care of the subject.